Contents lists available at ScienceDirect Epilepsy Research journal homepage: www.elsevier.com/locate/epilepsyres Detailed spectral profile analysis of electrocorticograms during freezing against penicillin-induced epileptiform discharges in the anesthetized rat Tatsuji Tokiwa a,b, ⁎ , Lev Zimin c , Takao Inoue d , Sadahiro Nomura d,e , Michiyasu Suzuki d , Takeshi Yamakawa f a Graduate School of Information Sciences, Hiroshima City University, Hiroshima, Japan b Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu, Japan c Graduate School of Information, Production and Systems, Waseda University, Fukuoka, Japan d Department of Neurosurgery, Yamaguchi University Graduate School of Medicine, Ube, Japan e Epilepsy Center, Yamaguchi University Hospital, Ube, Japan f Fuzzy Logic Systems Institute, Fukuoka, Japan ARTICLE INFO Keywords: Electrocorticogram Time-frequency analysis Delta wave Penicillin G-induced epileptiform discharge Cryoprobe Wistar rat ABSTRACT Objectives: Cryosurgery is an alternative technique for minimally invasive treatment of lesions. We have recently examined cryosurgery for epilepsy in animal models, and found that penicillin G (PG)-induced epileptiform discharges (EDs) mostly vanished after freezing. However, EDs were provoked again after insufficient freezing. Inadequate freezing is not visually detectable during and just after freezing and is not predictable beforehand. To manage this problem, we examined whether intraoperative monitoring of electrocorticograms (ECoGs) can predict recurrence of EDs after cryosurgery. Methods: A palm-sized cryoprobe system was applied to focal seizures in a Wistar rat model in which EDs were induced in advance by intracerebral injection of PG. During stable induction of EDs, the cryoprobe was carefully inserted into the epileptic region and this region was immediately frozen. After the series of prefreezing, freezing, and postfreezing, rats in which PG-induced EDs relapsed within 3 h were defined as the ED-relapsed (EDR) group, and other rats were defined as the ED-vanished (EDV) group. Time-frequency analysis was con- ducted on the ECoGs in each group through each freezing series. Results: Relapse of PG-induced EDs on ECoG after the freezing series was associated with the remaining power of the delta band in the freezing period more strongly in the EDR group than in the EDV group. Conclusions: Success or failure of the freezing procedure can be predicted by the specificity of the delta band of the ECoG obtained intraoperatively. 1. Introduction Cryosurgery is an alternative technique for minimally invasive re- section of lesions (Gage et al., 2009; Korpan, 2001) that is a simple procedure to perform, and has hemostatic (Ganz, 1974) and anesthetic (Schneider et al., 1985)effects. Cryosurgery has been primarily applied to the skin and breast (Korpan, 2001; Yiu et al., 2007), but rarely to the brain (Cooper, 1962, 1964; Hass and Taylor, 1953; Rand and Markham, 1964; Rowbotham et al., 1959; Tytus, 1961) because of the adverse effects of pathological deterioration. To verify the effectiveness of cryosurgery for neurosurgical operation, especially surgical treatment for intractable epilepsy, we recently proposed a newly developed palm- sized cryoprobe system (Tokiwa et al., 2015). The system was applied to a Wistar rat model of focal seizure, in which epileptiform discharges (EDs) were induced in advance by cortical application of the potent epileptogenic substance penicillin G (PG). In a series of experiments, we showed that PG-induced EDs could be eliminated at the onset of the freezing procedure. However, the EDs were occasionally provoked again after the freezing period due to inadequate freezing protocols (e.g., freezing speed, area, and temperature). These EDs were un- expected and were not visually detectable during freezing or im- mediately after freezing. In this study, we conducted time-frequency analysis of ECoGs in a freezing procedure series to define an approach to therapy using freezing. https://doi.org/10.1016/j.eplepsyres.2018.03.021 Received 30 July 2017; Received in revised form 30 January 2018; Accepted 28 March 2018 ⁎ Corresponding author at: Graduate School of Information Sciences, Hiroshima City University, Hiroshima, 731-3194, Japan. E-mail address: tokiwa@hiroshima-cu.ac.jp (T. Tokiwa). Abbreviations: ECoG, electrocorticogram; ED, epileptiform discharge; EDR, epileptiform discharge-relapsed; EDV, epileptiform discharge-vanished; FFT, fast Fourier transform; GABA, gamma-aminobutyric acid; IRDS, interictal regional delta slowing Epilepsy Research 143 (2018) 27–32 Available online 29 March 2018 0920-1211/ © 2018 Elsevier B.V. All rights reserved. T